Novel biopanning strategy to identify epitopes associated with vaccine protection

Barbara C. Bachler, Michael Humbert, Brisa Palikuqi, Siddappa Nagadenahalli Byrareddy, Samir K. Lakhashe, Robert A. Rasmussen, Ruth M. Ruprecht

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Identifying immune correlates of protection is important to develop vaccines against infectious diseases. We designed a novel, universally applicable strategy to profile the antibody (Ab) repertoire of protected vaccine recipients, using recombinant phages encoding random peptide libraries. The new approach, termed "protection-linked (PL) biopanning," probes the Ab paratopes of protected vaccinees versus those with vaccine failure. As proof of concept, we screened plasma samples from vaccinated rhesus macaques (RMs) that had completely resisted multiple mucosal challenges with R5-tropic simian-human immunodeficiency viruses (SHIVs). The animals had been immunized with a multicomponent vaccine (multimeric HIV-1 gp160, HIV-1 Tat, and SIV Gag-Pol particles). After PL biopanning, we analyzed the phagotopes selected for amino acid homologies; in addition to the expected Env mimotopes, one recurring motif reflected the neutralizing Ab epitope at the N terminus (NT) of HIV-1 Tat. Subsequent binding and functional assays indicated that anti-Tat NT Abs were present only in completely or partially protected RMs; peak viremia of the latter was inversely correlated with anti-Tat NT Ab titers. In contrast, highly viremic, unvaccinated controls did not develop detectable Abs against the same epitope. Based upon the protective effect observed in vivo, we suggest that Tat should be included in multicomponent HIV-1 vaccines. Our data highlight the power of the new PL-biopanning strategy to identify Ab responses with significant association to vaccine protection, regardless of the mechanism(s) or targets of the protective Abs. PL biopanning is also unbiased with regard to pathogens or disease model, making it a universal tool.

Original languageEnglish (US)
Pages (from-to)4403-4416
Number of pages14
JournalJournal of virology
Volume87
Issue number8
DOIs
StatePublished - Apr 1 2013

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epitopes
Epitopes
Vaccines
HIV-1
vaccines
Human immunodeficiency virus 1
Macaca mulatta
antibodies
Antibodies
HIV Envelope Protein gp160
Antibody Binding Sites
Peptide Library
AIDS Vaccines
Simian Immunodeficiency Virus
peptide libraries
Viremia
Neutralizing Antibodies
disease models
Bacteriophages
viremia

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Bachler, B. C., Humbert, M., Palikuqi, B., Byrareddy, S. N., Lakhashe, S. K., Rasmussen, R. A., & Ruprecht, R. M. (2013). Novel biopanning strategy to identify epitopes associated with vaccine protection. Journal of virology, 87(8), 4403-4416. https://doi.org/10.1128/JVI.02888-12

Novel biopanning strategy to identify epitopes associated with vaccine protection. / Bachler, Barbara C.; Humbert, Michael; Palikuqi, Brisa; Byrareddy, Siddappa Nagadenahalli; Lakhashe, Samir K.; Rasmussen, Robert A.; Ruprecht, Ruth M.

In: Journal of virology, Vol. 87, No. 8, 01.04.2013, p. 4403-4416.

Research output: Contribution to journalArticle

Bachler, BC, Humbert, M, Palikuqi, B, Byrareddy, SN, Lakhashe, SK, Rasmussen, RA & Ruprecht, RM 2013, 'Novel biopanning strategy to identify epitopes associated with vaccine protection', Journal of virology, vol. 87, no. 8, pp. 4403-4416. https://doi.org/10.1128/JVI.02888-12
Bachler BC, Humbert M, Palikuqi B, Byrareddy SN, Lakhashe SK, Rasmussen RA et al. Novel biopanning strategy to identify epitopes associated with vaccine protection. Journal of virology. 2013 Apr 1;87(8):4403-4416. https://doi.org/10.1128/JVI.02888-12
Bachler, Barbara C. ; Humbert, Michael ; Palikuqi, Brisa ; Byrareddy, Siddappa Nagadenahalli ; Lakhashe, Samir K. ; Rasmussen, Robert A. ; Ruprecht, Ruth M. / Novel biopanning strategy to identify epitopes associated with vaccine protection. In: Journal of virology. 2013 ; Vol. 87, No. 8. pp. 4403-4416.
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